LoDoCo2

2016

The aim of the LoDoCo2 (Low Dose Colchicine for secondary prevention of cardiovascular disease) trial was to investigate the effect of low dose colchicine (0,5 mg once daily) on the risk of myocardial infarction (fatal or non-fatal), stroke, or the need for coronary bypass or stent placement. While the precise mechanism through which colchicine mitigates major cardiovascular events remains incompletely understood, it is hypothesized that its anti-inflammatory effects contribute to risk reduction among patients with established atherosclerotic disease.

LoDoCo2 stands out in several respects. It represents a large-scale randomized clinical trial conducted entirely by a non-academic network of cardiologists and a consortium of pharmaceutical companies with a focus on drug repurposing. This trial underscores the potential value of older, often cost-effective medications in advancing the development of new innovative drugs.

The Research
Following a median follow-up period of 3 years, the addition of colchicine to standard treatment resulted in a 30% reduction in risk of myocardial infarction (fatal or non-fatal), stroke, or the need for coronary bypass or stent placement. Patients treated with colchicine exhibited similar side effects compared to those receiving a placebo. Furthermore, no interactions were found with other commonly used drugs such as (potent) statins.

In 2021, certain international guidelines had already incorporated colchicine into the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Subsequently, in 2023, the Food and Drug Administration (FDA) approved Lodoco® (colchicine) for reducing the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular (CV) death in adult patients with established atherosclerotic disease or multiple risk factors for CV disease. This approval was based on published data regarding the effects of colchicine on cardiovascular events, along with insights from the LoDoCo2 trial. The LoDoCo2 investigators anticipate that colchicine will become the standard treatment for patients with coronary artery disease.

The origin

The LoDoCo2 trial is based on based on LoDoCo, a small Australian trial that assessed the benefits of administration of a low dosis colchicine on coronary artery disease (CAD). Colchicine is a relatively inexpensive medication commonly used for the treatment of inflammatory disease, e.g. gout. The LoDoCo2 trial was executed with a similar protocol in Australia and the Netherlands.

LoDoCo2 is special in many ways; it is a large randomised clinical trial fully run by a non-academic network of cardiologists (WCN), funded by The Dutch Heart Foundation and ZonMw (Goed Gebruik Geneesmiddelen) and a consortium of pharmaceutical companies with focus on drug repurposing. Although the recruitment of patients already started before the start of the DCVA, the DCVA always has provided strong support, also in the route towards implementation. This drug-repurposing clinical trial shows that a collaborative statement from the DCVA and its partners is needed to change rules and regulations in order to make this effective, safe and cheap old treatment available for patients.

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Collaborators

Funded

Contact person:

A. Schut (Astrid)

Principal investigators

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FORSEE

2020
Clinical staff in hospital wards traditionally collect vital signs periodically to assess a patient's cardiorespiratory status, often with intervals of 6 to 10 hours. This method, known as spot-checking, has limitations due to its infrequent nature and dependence on contact sensors, which can be uncomfortable for patients, particularly during sleep. The Focus Recent advancements demonstrate that vital signs like heart rate, respiration rate, blood oxygen saturation, and temperature can be monitored remotely using camera-based methods, which are less invasive compared to contact sensors. This innovation could significantly enhance patient comfort by enabling continuous monitoring without the need for frequent interventions by clinical staff. Continuous monitoring also allows for trend analysis of vital signs, offering a comprehensive assessment of a patient's cardiorespiratory condition. Additionally, camera-based methods enable video context analysis, such as detecting patient movements or identifying pain through facial expression analysis. This project explores the use of continuous video monitoring as an unobtrusive method to predict and monitor patient deterioration or adverse events. The Research Initially, the feasibility and reliability of camera-based continuous monitoring will be evaluated using data from consenting patients in the ICU at Catharina Hospital in Eindhoven and healthy volunteers. Subsequently, robust technologies will be developed to automatically detect signs of patient deterioration by generating automated early warning scores based on measured vital signs. Throughout the project, feedback from clinical staff and patient experiences will inform the design and implementation of camera-based technologies and early warning systems. Origin This project is funded within the Innovative Medical Devices Initiative (IMDI) program 'Heart for Sustainable Care'. The focus of this program is the development of medical technology for the earlier detection, monitoring, and better treatment of cardiovascular diseases to ensure accessible healthcare and sufficient staffing. The program has been developed en funded by the Dutch Heart Foundation, ZonMw and NWO, who collaborate within the Dutch CardioVascular Alliance.
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Holland Hybrid Heart

2023
In the Netherlands, there are 250,000 patients with heart failure. Half of these patients die within five years. The best treatment: a donor heart. But: there is a great shortage of these. The Holland Hybrid Heart consortium is therefore working on an alternative: a robot heart, made of soft materials. The research We envision the treatment of patients with heart failure (HF) in such a way that the survival and quality of life of HF patients drastically increases. We aim to achieve this by developing a unique bioinspired total artificial heart that integrates soft robotics and tissue engineering (TE). In the long term, we foresee that this pioneering technology allows us to develop and bring to the clinic a full set of artificial motile organs and tissues that seamlessly integrate with the human body. This will be possible as the novel and exciting technologies underlying the artificial heart developed in this project - soft robotics and in situ TE - can be used to generate a broad range of artificial motile organs such as muscle structures (e.g., limbs), bowels or lungs: The motility and flexibility in shape and size of soft robots make them suitable for mimicking motile organs. Actuators can be embedded within the elastomeric matrix of these robots without compromising their malleable properties. In addition, embodied intelligence provides direct feedback on shape and force, enabling natural behaviour. Biocompatibility of these artificial organs is provided by TE inside the body (in situ) using biodegradable coatings or scaffolds. Such TE scaffolds are cell-free synthetic bio-resorbable implants or linings that can recruit or interact with cells from the bloodstream, leading to gradual replacement of the scaffold by fully endogenous, and thus biocompatible, tissue. Importantly, the cell-free and thus off-the-shelf availability of these scaffolds avoids the high costs and complex logistics inherent to pre-implantation in vitro TE. The Holland Hybrid Heart (HHH) consortium will push the development of these newly emerging technologies forward and combines soft robotics and in situ TE to generate the first biocompatible, soft actuated heart. This project will deliver Proof-of-Principle for full in vivo cardiac functionality of the artificial HHH in large animals. If successful, the HHH will be available for translation to the clinic as an effective treatment for advanced HF in patients and a valid alternative for moderately effective current HF therapies. This is a quantum leap forward in the treatment of HF. Origin A photo in the newspaper inspired Rotterdam heart specialist Jolanda Kluin to develop a robot heart. Kluin immediately contacted the interviewee in the article, Bas Overvelde, head of the Soft Robotic Matter group at Amolf, which develops soft robots. Could he perhaps also make a heart using soft robot techniques? Overvelde believed in it and a collaboration was born. Five years ago, they received a European subsidy of more than 3 million euros. This grant started the previous EU consortium, the EU Hybrid Heart. Last December (2023), Kluin received another 11 million euros from the Dutch government to continue the Holland hybrid heart project. The Holland Hybrid Heart has pivoted to meet the demands of that new grant and now only contains 15 Dutch consortium partners. The consortium is funded by NWA-ORC and the Dutch Heart Foundation. In-kind contributions are also provided by the DCVA, the Dutch Heart Foundation, TrailBlazers, SBMC, EVOS and EE-Labels. The executing academic partners are Erasmus MC, Amolf, TU Eindhoven, University of Twente, TU Delft and Saxion Applied University. This research is driven by patient needs and the Harteraad and Stichting Pulmonale Hypertensie will provide the connections to these patients.
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